Nicotinic Receptor Mutant Mice in the Study of Autonomic Function

Nicotinic acetylcholine receptors (nAChRs) have been implicated in Alzheimer's disease, Parkinson's disease, epilepsy, nicotine addiction, schizophrenia, and autonomic dysfunctions. Although nicotine may be used therapeutically either alone or in association with other drugs, its beneficial effects are limited by its addictive properties and a number of other side effects. A deeper understanding of nicotinic cholinergic mechanisms is necessary to develop nAChR ligands that are more selective, less toxic, and more therapeutically effective than nicotine.Although there has been significant progress identifying the nAChR subunits that form functional nAChRs, there is limited information associating the location and function of nAChR subtypes in the nervous system. Several groups have genetically engineered mice in which one or more genes encoding nAChR subunits has been deleted or altered. Mice with nAChR mutations targeted to subunits that are highly expressed in the CNS have brought insight into the nAChR mechanisms involved in nicotine addiction, analgesia, aging, and nicotine-induced behaviors. Mutations targeted to nAChR subunits that are highly expressed in the peripheral nervous system have opened a window on the complex mechanisms governing autonomic control of peripheral organs. This review examines nAChRs in the autonomic control of peripheral organ systems as gleaned from studies of nAChR mutant mice.